A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors

Cao, Junning; Zhang, Jian; Peng, Wei; Chen, Zhiyu; Fan, ST; Su, Weiguo; Li, Ké; Li, Jin

doi:10.1007/s00280-016-3069-8

Cited by 52 publications

(28 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In phase I trials, fruquintinib demonstrated good pharmacokinetic properties, tolerable safety, and promising anti-tumor activity against multiple tumor types [13]. A further two-regimen comparison study was carried out [14], and a regimen of 5 mg once daily oral dose on a 3-week-on/1-week-off treatment cycle was determined as the recommended phase II dose (RP2D).…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study

Bai

et al. 2017

J Hematol Oncol

Self Cite

View full text Add to dashboard Cite

BackgroundTo assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients.MethodsA phase Ib open-label study and phase II randomized, placebo-controlled trial compared the efficacy of fruquintinib plus best supportive care (BSC) with placebo plus BSC in mCRC patients with ≥2 lines of prior therapies. The primary endpoint was progression-free survival (PFS).ResultsIn the phase Ib study, 42 patients took fruquintinib 5 mg for 3 weeks on/1 week off. The median PFS was 5.80 months, and the median overall survival (OS) was 8.88 months. In the phase II study, 71 patients were randomized (47 to fruquintinib, 24 to placebo). PFS was significantly improved with fruquintinib plus BSC (4.73 months; 95% confidence interval [CI] 2.86–5.59) versus placebo plus BSC (0.99 months; 95% CI 0.95–1.58); (hazard ratio [HR] 0.30; 95% CI 0.15–0.59; P < 0.001). The median OS was 7.72 versus 5.52 months (HR 0.71; 95% CI 0.38–1.34). The most common grade 3–4 adverse events were hypertension and hand-foot skin reaction.ConclusionsFruquintinib showed a significant PFS benefit of 3.7 months in patients with treatment-refractory mCRC. The safety profile was consistent with that of VEGFR tyrosine kinase inhibitors. A randomized phase III confirmatory study in mCRC is underway.Trial registration NCT01975077 and NCT02196688 Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0384-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study

Bai

et al. 2017

J Hematol Oncol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fruquintinib, a highly potent and selective VEGFR 1/2/3 inhibitor, showed an acceptable safety profile and significant efficacy in a phase I study [ 14 ]. It is currently being evaluated in a randomized phase III study (FALUCA, NCT02691299, PI: Shun Lu, Shanghai Chest Hospital, China) that aims to compare fruquintinib with a placebo in NSCLC patients who either failed two lines of systemic chemotherapy or experienced intolerable toxicities.…”

Section: Introductionmentioning

confidence: 99%

Clinical trials of tyrosine kinase inhibitors for lung cancer in China: a review

2017

J Hematol Oncol

View full text Add to dashboard Cite

With the development of evidence-based medicine, clinical trials have become necessary for investigating and validating the efficacy of new treatments. Over the past 10 years, several clinical trials of new anticancer agents have been designed and launched in China; this has greatly promoted the development of novel agents as well as of innovative clinical study designs. However, despite the significant advances made in clinical trials for novel agents, improvements are still required. In this mini-review, we will summarize the ongoing clinical trials of small molecular inhibitors for the treatment of lung cancer in China, aiming specifically to highlight the active involvement of China in these clinical studies. Furthermore, we will discuss the urgent need for improvement of clinical trials and anticancer agent research in China.

show abstract

“…Fruquitinib, a selective inhibitor of VEGF receptors 1, 2 and 3, is being investigated in the "FRESCO" phase 3 trial in a Chinese refractory mCRC population naive to anti-VEGF therapy. 37,38 This is based on phase 2 data where fruquintinib improved median OS to 9.3 m, v 6.6 m with placebo [HR 0.65; 95% CI 0.51-0.83; p<0.001]. 38 The "FRESCO-2" trial is being conducted in a similar population but allows previous treatment with anti-VEGF mAB, TAS-102 or regorafenib.…”

Section: Emerging Therapies Anti-vegf Strategiesmentioning

confidence: 99%

<p>Refractory Metastatic Colorectal Cancer: Current Challenges and Future Prospects</p>

Lam¹,

Lum²,

Latham³

et al. 2020

CMAR

View full text Add to dashboard Cite

Despite advances, patients with metastatic colorectal cancer (mCRC) still have poor long-term survival. Identification of molecular subtypes is important to guide therapy through standard treatment pathways and holds promise for the development of new treatments. Following standard firstand second-line chemotherapy plus targeted agents, many patients retain a reasonable performance status, and thus are seeking further effective treatment to extend life and maintain symptom control. The challenge lies in selecting the most appropriate therapy in the third-and fourth-line settings, from a range of options including the relatively new oral agents TAS-102 and regorafenib, or rechallenge with previous chemotherapy or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mAB). Beyond this, therapy consists of trials involving novel agents and new combinations of treatments with theoretical synergy and/or non-overlapping toxicity. There is a great focus on enhancing immunogenicity in mCRC, to reflect the impressive results of immunotherapy drugs in the small cohort with mismatch repair deficient (dMMR) mCRC. Rare molecular subtypes of mCRC are increasingly being identified, including Her2-positive disease, NTRK fusions and others. Clinical trials exploring the efficacy of immunomodulatory and precision agents are plentiful and will hopefully yield clinically meaningful results that can be rapidly translated into routine care.

show abstract

A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors

Abstract: Fruquintinib showed an acceptable safety profile and preliminary evidence of anti-tumor activity in patients with advanced solid tumors. The recommended dose was determined to be either 4 mg QD on a continuous regimen or 5 mg QD on a 3-week-on/1-week-off regimen.

Cited by 52 publications

References 25 publications

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study

Clinical trials of tyrosine kinase inhibitors for lung cancer in China: a review

<p>Refractory Metastatic Colorectal Cancer: Current Challenges and Future Prospects</p>

Contact Info

Product

Resources

About